Phase I clinical studies will be conducted in cancer patients to evaluate the therapeutic effectiveness of uricase and two asparaginases modified to eliminate immunogenicity and yield extended and reproducible plasma circulating lives. These desirable therapeutic properties are produced by the covalent attachment of polyethylene glycol (PEG). PEG-uricase will be administered to patients with cancer-associated hyperuricemia and to patients with hyperuricemia that is consequence of radiation or chemotherapy for cancer. Plasma half-life and effectiveness in reducing plasma urate for extended periods of time will be evaluated. The anti-tumor effectiveness of PEG-asparginases from Eschericia coli and Vibrio succinogenes will be evaluated in a comprehensive Phase I study. Additional PEG-enzymes of potential use in cancer therapy are being evaluated in animal-tumor systems for their anti-tumor effectiveness when administered singly or in combination. These include PEG-arginase, PEG-methionase, and PEG-phenylalanine ammonialyase. Promising PEG-enzymes will be prepared in amounts sufficient for Phase I studies. Targeted PEG-enzymes are being developed for treatment of storage diseases or for other clinical problems that might be treated by a targeted enzyme. Targeting is accomplished by covalent attachment of a targeting molecule at the free end of PEG strands. Targeted PEG-0amyloglucosidase (glycogen storage diseases) and PEG-Beta-glucuronidase (acid mucopolysaccharide storage) will be tested in animals and cell culture. If successful, Phase I studies will be started. Modified methodology for effective glycolipid-degrading targeted PEG-enzymes is under development. Immunological studies are designed to explain the immunological changes that occur as increasing amounts of PEG are attached to selected immunogens and allergens. Our long-term objectives are (a) to develop from inexpensive exogenous sources a spectrum of therapeutic enzymes that can be used to treat cancer, hyperuricemia, storage diseases and other pathologies, and (b) to better understand the manner by which PEG moderates the immune response.